Background and Purpose-Assessment of cerebral autoregulation has been traditionally performed with static changes in arterial blood pressure. Newer dynamic methods require the induction of sudden drops in arterial blood pressure with the sudden release of bilateral thigh cuffs. An alternative method is proposed, based on the spontaneous variability of arterial blood pressure that does not require its manipulation. We compared this method with the established thigh cuff method in patients with carotid artery stenosis. Methods-Cerebral blood flow velocity (determined by transcranial Doppler) and arterial blood pressure (determined by noninvasive servo-controlled plethysmograph) were recorded in 20 patients with carotid artery stenosis and 18 age-matched controls. At rest, grading of dynamic autoregulation was estimated from the impulse response of the blood pressure-velocity dynamic relationship. This was compared with the autoregulatory index (ARI) provided by the thigh cuff method and with the degree of stenosis. The critical closing pressure was derived from the fitted models and was also correlated with degree of stenosis. Results-The 2 ARIs were significantly correlated (rϭ0.76) and reduced in subjects with carotid stenosis (baseline ARI, 3.65Ϯ3.11 versus 6.68Ϯ1.88, PϽ0.0001; thigh cuff ARI, 3.78Ϯ2.32 versus 6.35Ϯ1.06, PϽ10

This simple technique allows identification of impaired autoregulation in patients with carotid artery disease. It may allow identification of patients at risk from transient falls of blood pressure as may occur at the onset of antihypertensive therapy and during surgery. It may allow a subgroup of patients with asymptomatic carotid stenosis who are at risk of hemodynamic stroke to be identified.

Background and Purpose-Animal studies suggest that nitric oxide (NO) is important in basal cerebral blood flow (CBF) regulation and that it may mediate the vasodilatory response to carbon dioxide. We investigated its role in the human circulation using the NO synthase inhibitor N

Background Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence.Methods ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362.

Cerebral blood flow is maintained constant over a range of cerebral perfusion pressures by cerebral autoregulation. Impaired cerebral autoregulation may be important in the pathogenesis of cerebral ischaemia. The mechanisms mediating normal cerebral autoregulation in humans are poorly understood. We used a recently described transcranial Doppler technique, which allows non-invasive measurement of dynamic cerebral autoregulation, to test the hypothesis that nitric oxide mediates cerebral autoregulation. The rate of rise of middle cerebral artery blood flow velocity, compared with that of arterial blood pressure, was determined following a stepwise fall in arterial blood pressure, in order to calculate an autoregulatory index. The effect of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) on dynamic autoregulation was compared with that of noradrenaline titrated to result in a similar rise in blood pressure. Six healthy subjects were studied in each group. The mean (S.D.) change in autoregulatory index following noradrenaline at a similar pressor dose was significantly greater than the change following the L-NMMA bolus: 1. 1 (1.2) compared with -0.8 (0.8) for the left middle cerebral artery (P=0.002), and 1.1 (0.8) compared with -0.8 (0.8) for the right middle cerebral artery (P=0.002). There was no difference in the mean (S.D.) blood pressure increase resulting from the two agents: L-NMMA, 19.7 (7.4) mmHg; noradrenaline, 15.5 (4.8) mmHg (P=0.281). These results suggest that nitric oxide mediates at least part of the dynamic phase of cerebral autoregulation in humans. Reduced nitric oxide release may play a role in the impaired cerebral autoregulation seen in patients with, or at risk of, cerebral ischaemia.

Nitric oxide (NO) regulates basal CBF. In a number of animal models NO has been implicated in the mediation of the regional changes in CBF (rCBF) that accompany neuronal activation (vasoneuronal coupling). However, some results in animal models have failed to confirm this finding, and the validity of extrapolation to man from animal data is uncertain. To determine the contribution of NO to basal global CBF and activation-induced changes in rCBF, the authors have performed quantitative H2(15)O positron emission tomography (PET) studies before and after administration of the non-isoform-specific NO synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA), in 10 healthy male volunteers. Learning a novel sequence of finger movements was used as a paradigm to induce regional frontal cortex activation. The effect of NO synthase inhibition on the magnitude and pattern of activation was determined. Resting global CBF fell from 33.3 +/- 5.3 mL x 100 g(-1) x min(-1) at rest before L-NMMA, to 26.5 +/- 7.7 mL x 100 g(-1) x min(-1) after L-NMMA (P = 0.001). This fall was reversed by L-arginine administration. Learning sequential finger movements induced increases in rCBF in the left motor, right prefrontal, and bilateral premotor cortices. After NO synthase inhibition with L-NMMA, there was no change in this pattern of activation and no reduction in the magnitude of rCBF responses at the foci of maximal stimulation before and after L-NMMA. These findings confirm that NO production contributes to basal CBF regulation in man, but show that systemic NO synthase inhibition with L-NMMA does not impair regional vasoneuronal coupling.

Prolonged hemiparetic migraine aura can cause diagnostic confusion and be mistaken for ischaemic stroke occurring during the course of a migraine--'migrainous infarction'. We report a case of prolonged hemiparesis occurring during the course of a migraine attack. Though initially confused with migrainous infarction, we suggest with sequential magnetic resonance imaging, magnetic resonance angiography, diffusion, perfusion images and magnetic resonance spectroscopy that the hemiplegia was not of vascular origin and that the patient had sporadic hemiplegic migraine. We hypothesize that the mechanisms of sporadic hemiplegic migraine probably lie at a cellular level, similiar to familial hemiplegic migraine.

Experimental Study on the Genesis of Cerebral Vasospasm• The cerebral vasospasm produced by blood, fractions of blood, and blood-borne agents administered intracisternally was studied arteriographically to attain a better understanding of the genesis of vasospasm. The results indicate this phenomenon is multifarious in origin, involving a number of spasmogens. Whole blood, platelets, platelet extracts, some isolated components of platelets, plasma, thrombin, histamine, serotonin and prostaglandins Fi o , E2 and F 2a produced a significant incidence and duration of spasm. Norepinephrine and prostaglandin Ei were inactive. Spasm produced by arachidonic acid and red blood cells was of questionable significance.Compared to whole blood, thrombin usually produced spasm which was more delayed in onset while most other active substances produced a shorter-lived spasm. However, among the pure substances tested, serotonin, prostaglandin E2 and prostaglandin F 2o induced spasm in small doses which most nearly resembled that observed with whole blood.The hypothesis that the course of spasm depends upon synthesis of spasmogens by brain and blood is advanced. Prostaglandin synthesis plays a major role in this concept.